Deeptankar DeMazumder1, Worawan B Limpitikul2, Miguel Dorante2, Swati Dey2, Bhasha Mukhopadhyay2, Yiyi Zhang3, J Randall Moorman4, Alan Cheng2, Ronald D Berger2, Eliseo Guallar3, Steven R Jones2, Gordon F Tomaselli1. 1. Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA deep@jhmi.edu gtomasel@jhmi.edu. 2. Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA. 3. Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 4. Division of Cardiology, University of Virginia, Charlottesville, VA, USA.
Abstract
AIMS: The need for a readily available, inexpensive, non-invasive method for improved risk stratification of heart failure (HF) patients is paramount. Prior studies have proposed that distinct fluctuation patterns underlying the variability of physiological signals have unique prognostic value. We tested this hypothesis in an extensively phenotyped cohort of HF patients using EntropyXQT, a novel non-linear measure of cardiac repolarization dynamics. METHODS AND RESULTS: In a prospective, multicentre, observational study of 852 patients in sinus rhythm undergoing clinically indicated primary prevention implantable cardioverter-defibrillator (ICD) implantation (2003-10), exposures included demographics, history, physical examination, medications, laboratory results, serum biomarkers, ejection fraction, conventional electrocardiographic (ECG) analyses of heart rate and QT variability, and EntropyXQT. The primary outcome was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary outcome was composite events (appropriate ICD shock and all-cause mortality). After exclusions, the cohort (n = 816) had a mean age of 60 ± 13 years, 28% women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 ± 16% Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 ± 24 months, there were 134 appropriate shocks and 166 deaths. After adjusting for 30 exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyXQT) for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53-3.41), respectively. Addition of EntropyXQT to a model comprised of the exposures or SHFS significantly increased net reclassification and the ROC curve area. CONCLUSIONS: EntropyXQT measured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyXQT complements conventional risk predictors and has the potential for broad clinical application. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The need for a readily available, inexpensive, non-invasive method for improved risk stratification of heart failure (HF) patients is paramount. Prior studies have proposed that distinct fluctuation patterns underlying the variability of physiological signals have unique prognostic value. We tested this hypothesis in an extensively phenotyped cohort of HF patients using EntropyXQT, a novel non-linear measure of cardiac repolarization dynamics. METHODS AND RESULTS: In a prospective, multicentre, observational study of 852 patients in sinus rhythm undergoing clinically indicated primary prevention implantable cardioverter-defibrillator (ICD) implantation (2003-10), exposures included demographics, history, physical examination, medications, laboratory results, serum biomarkers, ejection fraction, conventional electrocardiographic (ECG) analyses of heart rate and QT variability, and EntropyXQT. The primary outcome was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary outcome was composite events (appropriate ICD shock and all-cause mortality). After exclusions, the cohort (n = 816) had a mean age of 60 ± 13 years, 28% women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 ± 16% Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 ± 24 months, there were 134 appropriate shocks and 166 deaths. After adjusting for 30 exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyXQT) for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53-3.41), respectively. Addition of EntropyXQT to a model comprised of the exposures or SHFS significantly increased net reclassification and the ROC curve area. CONCLUSIONS: EntropyXQT measured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyXQT complements conventional risk predictors and has the potential for broad clinical application. Published on behalf of the European Society of Cardiology. All rights reserved.
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